1. Field of the Invention
This invention relates generally to bioactive proteins, peptides and enzymatic hydrolysates from rice bran and use thereof, and more particularly to a purified, unmodified and modified bioactive pentapeptide from heat stabilized defatted rice bran having anti-cancer, anti-obesity, anti-Alzheimer and other health-promoting activities. The bioactive pentapeptides can be incorporated as an active ingredient into pharmaceutical, nutraceutical and food compositions.
2. Description of the Related Art
The treatment of cancer, obesity-related and age-related chronic diseases are life-long and can have side effects. Americans are supplementing traditional health care by turning to nutraceuticals and functional foods. Nutraceuticals are considered safe, effective and ingestible for a lifetime without toxicity, reversibly inhibiting type and, also amenable to clinical trials. These, when proven effective, can function as alternatives to high-cost prescriptions, and could be the next generation natural anti-disease agents delivered at low cost and high efficacy. The use of nutraceuticals in foods, beverages and supplements is well established in Japan and is gaining interest in the United States.
In the United States, cancer is the second most leading cause of death. The Centers for Disease Control and Prevention (CDC) estimated nearly 1.4 million new cases of cancer in 2008 and half a million deaths due to cancer occurred in 2007. Colorectal cancer is the second leading cause of cancer-related death in the United States. Over the past decade, the incidence of colorectal cancer has not decreased, and hence there has been no improvement in the mortality rate. Treatment and preventive options for colorectal cancer mainly focus on early detection. There is evidence that dietary components are one of the most important environmental factors in the cause of the colorectal cancer and hence may act as suitable markers or dietary determinants, which when modified and prepared in a biofunctional form can serve as bioactive compounds in reducing the incidence of colorectal cancers. Liver cancer is the most common cancer type in developing countries, but is less common (2% of cancer deaths) in United States, affecting twice as many men as women. The American Cancer Society has estimated 21,370 new cases in 2008 with 18,410 liver-cancer-related deaths in the United States in 2007. Chemotherapy, radiotherapy and liver transplantation are the treatment options available for treating liver cancer. As alternative treatment, to reduce the risk of developing cancer, the focus is on identifying compounds present in natural foods that could bear anti-liver cancer properties.
In addition to cancer, the risk of chronic complications from obesity-related diseases is a leading cause of death in the United States. The growing epidemics of type-2 diabetes and cardiovascular disease are linked to obesity, and in fact, nearly 90% of diabetics are caused by obesity. Consequently, obesity has triggered impaired glucose tolerance in nearly 197 million people worldwide. Estimated cases of diabetes in the United States currently stand at 19.2 million comprising 30-40% of world's type-2 diabetics. Roughly 63.1% of Americans have been identified to be obese with a basal metabolic index (BMI) of at least 25.0. In particular, childhood obesity in the United States has tripled in the past two (2) decades.
Following the ranks of cancer and cardiovascular disease and their related complications in causing death, is a neurological disorder, Alzheimer's disease. It has been thought that blood vessel damage in the brain, most likely to occur in patients with diabetes and high cholesterol, can lead to symptoms of Alzheimer's disease and, preventing these states can reduce the risk of developing Alzheimer's disease. One (1) in eight (8) persons aged 65-85 and nearly half of persons over age 85 have Alzheimer's disease. In 2011, baby boomers (those born between 1946 and 1964) will begin turning 65, reaching the age that stratifies greatest risk for Alzheimer's disease. To reduce the risk for Alzheimer's disease, many have turned to alternative treatments based on compounds present in natural foods that could bear anti-Alzheimer's disease properties.
Several bioactive components in nutraceuticals have demonstrated anti-oxidant, anti-obesity, anti-angiogenic and anti-hypertensive activities and hypocholesterolemic and immunomodulatory effects. Peptides and proteins from food sources can aid in cancer prevention and treatment. For example, whey proteins and α-lactalbumin have been shown to inhibit colon cell proliferation. Cereal grains and their components are widely investigated for the presence of bioactive components to be used in nutraceuticals. Cereal grains are known to possess high-quality protein, which when consumed, are broken down by gastrointestinal (GI) proteolytic enzymes to release bioactive peptides. Cereal grains including rice, wheat and legumes, including soybeans, and their respective components, have been investigated for the presence of bioactive proteins and peptides. For example, Oryzatensin, an ileum-contracting bioactive peptide obtained from rice albumin, has been shown to have an immuno-stimulatory role. Similarly, proteolytic hydrolysis of soybean protein using Alcalase and Proteinase S enzymes resulted in peptides that were anti-hypertensive and anti-oxidative, respectively. Rice and its components have also been studied to exert specific anti-disease properties, such as anti-oxidative, anti-carcinogenic and anti-mutagenic. Constituents such as proteins and peptides from rice or co-products of rice milling, however, have only been studied to a limited extent.
Enzymatic hydrolysis has been one of the main approaches to produce bioactive peptides from soybean, wheat, corn, rice, barley, buckwheat and sunflower proteins. The potential bioactive nature of components of rice, however, is not well known, including the bran portion, which is nutritionally beneficial but used as a low cost animal feed. It is also important that the peptides be resistant to GI environment when ingested for being metabolically bioactive.
Rice bran is a cheap co-product of rough rice milling having nutrients including B vitamins, minerals, and fiber, including oil, which has health benefits. It is being used as a low-cost animal feed and the state of Arkansas contributes over 50% of the overall rice production in the United States. Defatted rice bran has approximately 20% protein, with the proteins and their peptide fragments being complexed within carbohydrates and lipids providing difficulties in protein extraction.
It is therefore desirable to provide bioactive proteins, peptides and enzymatic hydrolysates from rice bran and use thereof.
It is further desirable to provide a purified, unmodified and modified bioactive pentapeptide from heat stabilized defatted rice bran having anti-cancer, anti-obesity, anti-Alzheimer and other health-promoting activities.
It is yet further desirable to provide bioactive pentapeptides that can be incorporated as an active ingredient into pharmaceutical, nutraceutical and food compositions.
It is still further desirable to provide bioactive pentapeptides having unique sequences that renders its bioactive nature, which can enhance glucose uptake into cells, act to sequester bad cholesterol and fatty acids accumulating in excessive BMI states, or even mitigate molecular events taking place in neuronal cells during the onset of Alzheimer's disease.